Tropical deforestation causes large reductions in observed precipitation.

Tropical forests play a critical role in the hydrological cycle and can influence local and regional precipitation1. Previous work has assessed the impacts of tropical deforestation on precipitation, but these efforts have been largely limited to case studies2. A wider analysis of interactions between deforestation and precipitation-and especially how any such interactions might vary across spatial scales-is lacking. Here we show reduced precipitation over deforested regions across the tropics. Our results arise from a pan-tropical assessment of the impacts of 2003-2017 forest loss on precipitation using satellite, station-based and reanalysis datasets. The effect of deforestation on precipitation increased at larger scales, with satellite datasets showing that forest loss caused robust reductions in precipitation at scales greater than 50 km. The greatest declines in precipitation occurred at 200 km, the largest scale we explored, for which 1 percentage point of forest loss reduced precipitation by 0.25 ± 0.1 mm per month. Reanalysis and station-based products disagree on the direction of precipitation responses to forest loss, which we attribute to sparse in situ tropical measurements. We estimate that future deforestation in the Congo will reduce local precipitation by 8-10% in 2100. Our findings provide a compelling argument for tropical forest conservation to support regional climate resilience.

Trends in childhood body mass index between 1936 and 2011 showed that underweight remained more common than obesity among 398 970 Danish school children.

AIM: To examine trends in all body mass index (BMI) groups in children from 1936 to 2011. METHODS: We included 197 694 girls and 201 276 boys from the Copenhagen School Health Records Register, born between 1930 and 1996, with longitudinal weight and height measurements (6-14 years). Using International Obesity Task Force criteria, BMI was classified as underweight, normal-weight, overweight and obesity. Sex- and age-specific prevalences were calculated. RESULTS: From the 1930s, the prevalence of underweight was stable until a small increase occurred from 1950 to 1970s, and thereafter it declined into the early 2000s. Using 7-year-olds as an example, underweight changed from 10% to 7% in girls and from 9% to 6% in boys during the study period. The prevalence of overweight plateaued from 1950 to 1970s and then steeply increased from 1970s onwards and in 1990-2000s 15% girls and 11% boys at 7 years had overweight. The prevalence of obesity particularly increased from 1980s onwards and in 1990-2000s 5% girls and 4% boys at 7 years had obesity. These trends slightly differed by age. CONCLUSION: Among Danish schoolchildren, the prevalence of underweight was greater than overweight until the 1980s and greater than obesity throughout the period. Thus, monitoring the prevalence of childhood underweight remains an important public health issue.

Can Patient-centered Education and Pain Management Delivered by Coaches Improve Pain Outcomes After Orthopaedic Trauma? A Randomized Trial.

BACKGROUND: Pain after orthopaedic trauma is complex, and many patients who have experienced orthopaedic trauma are at increased risk for prolonged opioid utilization after the injury. Patient-centered interventions capable of delivering enhanced education and opioid-sparing pain management approaches must be implemented and evaluated in trauma care settings to improve pain outcomes and minimize opioid-related risks. QUESTIONS/PURPOSES: Does personalized pain education and management delivered by coaches (1) improve pain-related outcomes, (2) reduce opioid consumption, and (3) improve patient-reported outcome measures (Patient-Reported Outcomes Measurement Information System [PROMIS] scores) compared to written discharge instructions on pain management and opioid safety? METHODS: This clinical trial aimed to examine the effect of a personalized pain education and management intervention, delivered by paraprofessional coaches, on pain-related outcomes and opioid consumption compared with usual care (written discharge instructions on pain management and opioid safety). Between February 2021 and September 2022, 212 patients were randomized to the intervention (49% [104]) or control group (51% [108]). A total of 31% (32 of 104) and 47% (51 of 108) in those groups, respectively, were lost before the minimum study follow-up of 12 weeks or had incomplete datasets, leaving 69% (72 of 104) and 53% (57 of 108) for analysis in the intervention and control group, respectively. Patients randomized to the intervention worked with the paraprofessional coaches throughout hospitalization after their orthopaedic injury and at their 2-, 6-, and 12-week visits with the surgical team after discharge to implement mindfulness-based practices and nonpharmacological interventions. Most participants in the final sample of 129 identified as Black (73% [94 of 129]) and women (56% [72 of 129]), the mean Injury Severity score was 8 ± 4, and one-third of participants were at medium to high risk for an opioid-use disorder based on the Opioid Risk Tool. Participants completed surveys during hospitalization and at the 2-, 6-, and 12-week follow-up visits. Surveys included average pain intensity scores over the past 24 hours measured on the pain numeric rating scale from 0 to 10 and PROMIS measures (physical functioning, pain interference, sleep disturbance). Opioid utilization, measured as daily morphine milligram equivalents, was collected from the electronic health record, and demographic and clinical characteristics were collected from self-report surveys. Groups were compared in terms of mean pain scores at at the 12-week follow-up, daily morphine milligram equivalents both during inpatient and at discharge, and mean PROMIS scores at 12 weeks of follow-up. Additionally, differences in the proportion of participants in each group achieving minimum clinically important differences (MCID) on pain and PROMIS scores were examined. For pain scores, an MCID of 2 points on the pain numeric rating scale assessing past 24-hour pain intensity was utilized. RESULTS: We found no difference between the intervention and control in terms of mean pain score at 12 weeks nor in the proportions of patients who achieved the MCID of 2 points for 24-hour average pain scores (85% [61 of 72] versus 72% [41 of 57], respectively, OR 2.2 [95% confidence interval (CI) 0.9 to 5.3]; p = 0.08). No differences were noted in daily morphine milligram equivalents utilized between the intervention and control groups during hospitalization, at discharge, or in prescription refills. Similarly, we observed no differences in the proportions of patients in the intervention and control groups who achieved the MCID on PROMIS Physical Function (81% [58 of 72] versus 63% [36 of 57], respectively, OR 2.2 [95% CI 0.9 to 5.2]; p = 0.06). We saw no differences in the proportions of patients who achieved the MCID on PROMIS Sleep Disturbance between the intervention and control groups (58% [42 of 72] versus 47% [27 of 57], respectively, OR 1.4 [95% CI 0.7 to 3.0]; p = 0.31). The proportion of patients who achieved the MCID on PROMIS Pain Interference scores did not differ between the intervention and the control groups (39% [28 of 72] versus 37% [21 of 57], respectively, OR 1.1 [95% CI 0.5 to 2.1]; p = 0.95). CONCLUSION: In this trial, we observed no differences between the intervention and control groups in terms of pain outcomes, opioid medication utilization, or patient-reported outcomes after orthopaedic trauma. However, future targeted research with diverse samples of patients at increased risk for poor postoperative outcomes is warranted to ascertain a potentially meaningful patient perceived effect on pain outcomes after working with coaches. Other investigators interested in this interventional approach may consider the coach program as a framework at their institutions to increase access to evidence-based nonpharmacological interventions among patients who are at increased risk for poor postoperative pain outcomes. Smaller, more focused programs connecting patients to coaches to learn about nonpharmacological pain management interventions may deliver a larger impact on patient's recovery and outcomes. LEVEL OF EVIDENCE: Level I, therapeutic study.

Radiographic Prediction of Soft Tissue Injury Associated with Tibial Plateau Fractures: The Direction of Articular Depression Matters.

This investigation aimed to evaluate the impact of coronal articular fragment displacement of Schatzker type II tibial plateau fractures on concomitant soft tissue knee injuries. One hundred consecutively treated patients were included. Depression depth and coronal articular fragment displacement were measured radiographically, and medial collateral ligament (MCL) and lateral meniscus (LM) injury, and pain and range of motion (ROM) on final follow up, were recorded. Multivariable regression was then performed. Coronal articular fragment displacement was medially and laterally hinged in 74% and 26% of patients, respectively. MCL injuries were significantly higher in the lateral hinge group (odds ratio [OR]: 3.25; confidence interval [CI]: 1.07 to 9.84; p = 0.03). No difference was found in LM injury incidence and amount of articular depression between groups. At final follow-up, average pain and ROM was similar between groups. Findings demonstrate a significant correlation between laterally hinged articular depression in Schatzker II tibial plateau fractures and concomitant MCL injury. (Journal of Surgical Orthopaedic Advances 32(4):270-275, 2023).

Wilson's disease - a tricky diagnosis on the acute take.

Wilson's disease is a rare genetic disorder that affects copper metabolism in the body, leading to excess copper accumulation in various organs, including the liver and brain. It often presents to both primary and secondary care, with a combination of liver disease and neurological or psychiatric symptoms, but the presentation can be highly variable. Early recognition and treatment of Wilson's disease is important to prevent critical hepatic and neurological complications. In this case report, we describe the presentation of an 18-year-old male university student with a combination of dysphagia, tremors, and slurred speech, which progressed over several months. Through a series of investigations, the patient was diagnosed with Wilson's disease and received appropriate treatment. This report highlights the importance of considering Wilson's disease in patients with a wide range of symptoms and the need for a pragmatic approach to diagnosis, including routine and additional testing as necessary.

[18F]Sodium fluoride PET-MRI detects increased metabolic bone response to whole-joint loading stress in osteoarthritic knees.

OBJECTIVE: Altered joint function is a hallmark of osteoarthritis (OA). Imaging techniques for joint function are limited, but [18F]sodium fluoride (NaF) PET-MRI may assess the acute joint response to loading stresses. [18F]NaF PET-MRI was used to study the acute joint response to exercise in OA knees, and compare relationships between regions of increased uptake after loading and structural OA progression two years later. METHODS: In this prospective study, 10 participants with knee OA (59 ± 8 years; 8 female) were scanned twice consecutively using a PET-MR system and performed a one-legged squat exercise between scans. Changes in tracer uptake measures in 9 bone regions were compared between knees that did and did not exercise with a mixed-effects model. Areas of focally large changes in uptake between scans (ROIfocal, ΔSUVmax > 3) were identified and the presence of structural MRI features was noted. Five participants returned two years later to assess structural change on MRI. RESULTS: There was a significant increase in [18F]NaF uptake in OA exercised knees (SUV P < 0.001, KiP = 0.002, K1P < 0.001) that differed by bone region. CONCLUSION: There were regional differences in the acute bone metabolic response to exercise and areas of focally large changes in the metabolic bone response that might be representative of whole-joint dysfunction.

Birthweight, body size, and growth during childhood and risks of rheumatoid arthritis: a large Danish cohort study.

OBJECTIVES: Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA. METHOD: A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930-1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed. RESULTS: During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4-9% and 6-10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19-1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA. CONCLUSIONS: Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.

Divergent Representation of Precipitation Recycling in the Amazon and the Congo in CMIP6 Models.

Moisture evaporated from the land contributing to precipitation in a given area is known as precipitation recycling and needs to be accurately represented in climate models. The Amazon and Congo basins are reported to have the highest precipitation recycling rates globally, but model representation has not yet been assessed over these regions. We evaluated recycling over the Amazon and Congo in 45 Coupled Model Intercomparison Project Phase 6 models. Regional annual means from models and reanalyzes agreed well over both basins. Models captured seasonal variation in recycling over the Congo but there was a large-scale underestimation of recycling during the Amazon dry-to-wet transition season relative to ERA5, caused by models underestimating Amazon evapotranspiration and overestimating incoming wind speed and associated water vapor imports. Both regions show robust declines in precipitation recycling over the next century under future climate-change scenarios. Our results suggest models may underestimate impacts of deforestation on regional precipitation in the Amazon.

A controlled evaluation of the effect of social prescribing programs on loneliness for adults in Queensland, Australia (protocol).

BACKGROUND: In social prescribing, link workers support individuals whose persistent health problems are exacerbated by loneliness by connecting them to community-based social activities. This approach is well established in the UK and is gaining attention in Australia. However, a major limitation of research to date has been a lack of theoretically informed and rigorous evaluations of social prescribing. We will address these points in this study, applying a social identity framework to examine the effects of group-based social prescribing (SP) activity compared to primary care treatment as usual (TAU). METHODS: Ninety participants experiencing loneliness recruited from primary care services and community centres across five sites in Southeast Queensland will be assigned to one of two conditions (SP, TAU) and assessed at two timepoints (baseline, + 8 weeks). Individuals will be aged 18 years and over, have sufficient English language skills to provide consent, and at the time of recruitment they will not be experiencing acute symptoms or social issues that require urgent intervention. Primary outcomes are loneliness, mental well-being, and health service use (total number of GP, hospital, and allied health visits in the past 3 months). Secondary outcomes will assess social group processes, including number of important social groups, new group identification, multiple identity compatibility, and group-based support and emotion regulation. DISCUSSION: This study will provide comprehensive data about the extent to which, and how, social prescribing to community-based group activities may help people to feel less lonely, more socially integrated, and healthy over the first 8 weeks. If effective, this social identity-informed model of social prescribing can be disseminated in communities across Australia. TRIAL REGISTRATION: ANZCTR, Registered 8 June 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000801718.aspx.

Hard to Swallow Results.

The American Neurogastroenterology and Motility Society (ANMS) proposed quality measures (QMs) for performance and interpretation of esophageal manometry (EM). We implemented a quality improvement (QI) study at a large community hospital to assess and improve procedural adherence and interpretation of EM studies based on the ANMS QMs using the Chicago Classification 3.0 (CC) Guidelines. For pre-intervention, three motility independent reviewers reinterpreted 60 EM studies conducted by community gastroenterologists without Tier II-III motility training from October to December 2018 for compliance with pre-procedural, procedural, and data interpretation ANMS QMs. In December 2018, we developed a pre-procedural form, educated nurses on EM procedural compliance, and provided preliminary pre-intervention results to gastroenterologists along with literature utilizing the CC 3.0 Guidelines. For post-intervention, we reinterpreted 54 EM studies from January to August 2019 and investigated whether they met QMs for data interpretation with respect to the CC Guidelines and resulted in appropriate treatment. We found a statistically significant improvement in procedural compliance among nursing staff for 30 s of swallows (76% post-intervention versus 12% pre-intervention, p < 0.001) and 7 evaluable swallows (94% post-intervention versus 53% pre-intervention, p < 0.001). However, quality metrics within data interpretation by physicians post-intervention showed mixed results. An incorrect diagnosis was made in 50% (n = 27)) of studies with 72% (n = 39) having at least one missing item based on the CC. The most missed diagnosis was fragmented peristalsis (30%, n = 29). Among the 39% (n = 21) of surgery referrals, 24% (n = 5) were incorrectly referred. Our study shows poor data interpretation by community gastroenterologists without formal motility training despite adequate performance by nursing staff. This further supports the need for a national ANMS certification process for formal HRM education.

Integration of Life Care Specialists Into Orthopaedic Trauma Care to Improve Postoperative Outcomes: A Pilot Study.

BACKGROUND: AIM: This pilot study assessed the feasibility and impact of integrating a Life Care Specialist (LCS) into orthopaedic trauma care. DESIGN: This was a prospective feasibility single group pilot study at a level 1 trauma center. METHOD: The LCS is a paraprofessional behavior-based "pain coach" and delivered patient-centered opioid safety education, trained participants on nonpharmacologic pain management approaches, conducted opioid risk assessments, and coordinated care. Numeric Rating Scale pain scores were assessed on admission, at discharge, and at 2-week follow-up. Daily morphine milligram equivalents (MME) during hospitalization, opioid medication use at 2-weeks, and patient satisfaction were recorded. T test compared mean morphine milligram equivalents (MME) to historical orthopaedic trauma patient population's mean dosage at discharge from the study site. Generalized linear models assessed pain scores over time. RESULTS: Twenty-two percent of 121 total participants met criteria for moderate to severe risk of opioid misuse at initial hospitalization. On average, 2.8 LCS pain management interventions were utilized, most frequently progressive muscle relaxation (80%) and sound therapy (48%). Mean inpatient MME/day was 40.5, which was significantly lower than mean historical MME/day of 49.7 (p < .001). Pain scores improved over time from admission to 2-weeks postoperatively (p < .001). Nearly all participants agreed that the LCS was helpful in managing pain (99%). CONCLUSIONS: The findings indicate feasibility to integrate LCS into orthopaedic trauma care, evident by participant engagement and satisfaction, and that LCS serve as valuable resources to assist with pain management and opioid education.

AD and its comorbidities: An obstacle to develop a clinically efficient treatment?

Whilst the development of new drugs designed for the treatment of Alzheimer's disease (AD) has been widely publicised, we do not yet have treatments that are proven to slow the progression of AD. The decision taken by the US Food and Drug Administration (FDA) to grant a licence for the use of aducanumab, based on the premise that ß-amyloid removal would result in downstream benefits rather than demonstration of cognitive efficacy per se contrasts with that made by the European Medicines Agency (EMA), who declined to grant a licence, citing lack of evidence of clinical improvement, and a failure to demonstrate that the treatment was sufficiently safe. Multiple factors have complicated the search for new and effective treatments for the management of AD. It is a complex neurodegenerative condition in which multiple comorbidities are common in the affected population. However, such conditions are commonly exclusion criteria in clinical trials for new treatments. Here we discuss how some of these comorbidities impact the development of clinically efficient treatments for AD. Firstly, we will examine what is meant by AD, and how definitions of this condition have changed and continue to evolve. Secondly, we describe some of the most important comorbid conditions accompanying and in some cases mimicking AD. Finally, we will examine how the inclusion, or exclusion, of these conditions from AD research may have had an effect on treatment trials, the implications of co-morbidities on "real-life" use of novel therapeutics especially when these have been trialled in patients with relatively pure disease, and how clinical trials may need to adapt to account for comorbidities in the future.

Physical Activity and Sedentary Behavior of Elderly Populations during Confinement: Results from the FRENCH COVID-19 ONAPS Survey.

Introduction: A national confinement was imposed in France in March 2020 during 55 days to prevent the spread of the virus and protect vulnerable people such as older individuals. This study aimed to describe the movement behaviors, and their determinants, of elderly people (≥ 65 years) during the confinement.Methods: An online survey was conducted from April 1st, 2020 to May 6th, 2020 by the National Observatory for Physical Activity and Sedentary behaviors. This study compared the level of physical activity (PA), sitting and screen time before and during the confinement and identified the impact of initial PA, sedentary profiles of the participants and housing conditions.Results: 1,178 people were included in this study. Reaching PA recommendations before lock-down was associated with the change in PA level during lock-down (p < .001). Besides, geographic location was associated with the change in PA, sitting time and screen time during lock-down (respectively p = .03, p = .02, p = .02).Conclusion: This study confirm the negative impact of confinement on senior movement behaviors, whether or not they met with public health recommendations prior to the pandemic. The housing conditions of older people must be also taken into future public health policies.

Cracked Tooth Syndrome: Assessment, Prognosis and Predictable Management Strategies.

Cracked tooth syndrome (CTS) is a common presentation in general practice. The diagnosis and management of teeth with CTS may be difficult due to the unknown extent of the crack. This article reviews the aetiology, diagnosis, management and prognosis of teeth with CTS. A thorough examination is required to effectively assess CTS. Intervention should aim to relieve symptoms and brace the remaining tooth structure effectively against further flexion. Restored teeth with CTS have a guarded prognosis due to the risk of further crack propagation, but the chances of survival at 5-years is acceptable (74.1-96.8%).

Poetry and possible selves: Crisis theory with/in teacher education programs.

The COVID-19 pandemic has altered the educational landscape. This article offers the model, Crisis Theory with/in Teacher Education Programs (CT-TEP), which examines how the interplay of preservice teachers' stressors and personal coping strategies filtered through their identity provides teacher educators strategies for helping students persevere through crises. Data collected in one teacher education program during the spring 2020 COVID-19 shutdown across the United States illuminates preservice teachers' present and possible selves, through a series of poems demonstrating emotions and coping strategies of student-participants. Implications for teacher educators to focus on possible selves with/in teacher education classrooms as a mechanism for understanding emotional health and well-being is discussed.

Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan: evidence from two longitudinal cohort studies 15 years apart.

BACKGROUND: Oshikhandass is a rural village in northern Pakistan where a 1989-1991 verbal autopsy study showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989-1996; here we assess improvements in under-5 mortality, diarrhea, and pneumonia over this period and 15 years later. METHODS: Two prospective open-cohort studies in Oshikhandass from 1989 to 1996 (Study 1) and 2011-2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines, conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia. RESULTS: Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births (LB) between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.8 deaths/ 1000 LB). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6 to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and housing materials was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia in Study 1. CONCLUSIONS: We report a 4-fold decrease in overall childhood mortality, and a 2-fold decrease in childhood morbidity from diarrhea and pneumonia in a remote rural village in Pakistan between 1989 and 2014. We conclude that significant, sustainable improvements in child health may be achieved through improved socioeconomic status and promoting interactions between locally engaged health workers and the community, but that continued efforts are needed to improve health worker training, supervision, and the rational use of medications. TRIAL REGISTRATION: Not Applicable.

An evaluation of continuous subcutaneous infusions across seven NHS acute hospitals: is there potential for 48-hour infusions?

BACKGROUND: Continuous subcutaneous infusions (CSCIs) are commonly used in the United Kingdom as a way of administering medication to patients requiring symptom control when the oral route is compromised. These infusions are typically administered over 24 h due to currently available safety data. The ability to deliver prescribed medication by CSCI over 48 h may have numerous benefits in both patient care and health service resource utilisation. This service evaluation aims to identify the frequency at which CSCI prescriptions are altered at NHS Acute Hospitals. METHODS: Pharmacists or members of palliative care teams at seven acute NHS hospitals recorded anonymised prescription data relating to the drug combination(s), doses, diluent and compatibility of CSCIs containing two or more drugs on a daily basis for a minimum of 2 days, to a maximum of 7 days. RESULTS: A total of 1301 prescriptions from 288 patients were recorded across the seven sites, yielding 584 discrete drug combinations. Of the 584 combinations, 91% (n = 533) included an opioid. The 10 most-common CSCI drug combinations represented 37% of the combinations recorded. Median duration of an unchanged CSCI prescription across all sites was 2 days. CONCLUSION: Data suggests medication delivered by CSCI over 48 h may be a viable option. Before a clinical feasibility study can be undertaken, a pharmacoeconomic assessment and robust chemical and microbiological stability data will be required, as will the assessment of the perceptions from clinical staff, patients and their families on the acceptability of such a change in practice.

Diverse Reactivity of Dienes with Pentaphenylborole and 1-Phenyl-2,3,4,5-Tetramethylborole Dimer.

The reactions of a monomeric borole and a dimeric borole with 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene were investigated. The monomeric borole reacted at ambient temperature whereas heat was required to crack the dimer to form the monomer and induce reactivity. 2,3-Dimethyl-1,3-butadiene reacts to give diverse products resulting from a cycloaddition process with the B-C moiety of the boroles acting as a dienophile, followed by rearrangements to furnish bicyclic species. For 1,3-cyclohexadiene, a [4+2] process is observed in which 1,3-cyclohexadiene serves as the dienophile and the boroles as the diene partner. The experimental results are corroborated with mechanistic theoretical calculations that indicate boroles can serve as either a diene or dienophile in cycloaddition reactions with dienes.

Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: a systematic review of intervention studies.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS) that can be tracked through biomarkers of disease status. We investigated the effects of exercise on MS biomarkers associated with CNS status including imaging, blood-brain barrier (BBB) function and neurotrophic factors. METHODS: We conducted open-dated searches of Scopus, Medline, EMBASE and the Cochrane Library. We included studies written in English describing interventions of exercise that measured one or more of the biomarkers associated with MS published up to October 2018. RESULTS: We located a total of 3012 citations through searches in electronic databases. Of these, 16 studies were eligible for review; six studies focused on magnetic resonance imaging (MRI) markers, nine studies focused on neurotrophic factors and three studies focused on BBB function markers. It is of note that two studies included both neurotrophic factor and BBB function markers and are therefore included across categories of biomarkers in this review. The existing evidence from MRI studies confirmed that exercise training can improve CNS integrity and function. There is evidence of a positive effect of exercise training on modulation of BBB permeability markers and brain-derived neurotrophic factor. CONCLUSIONS: Exercise successfully improves MRI outcomes and peripheral biomarkers (i.e. brain-derived neurotrophic factor) in people with MS. This suggests that exercise can be recommended as an adjuvant therapy for MS treatment. This conclusion is tempered by some methodological limitations including small sample sizes and high drop-out rates in the reviewed studies.